The long-term goal of this SCOR investigating cute lung injury (ALI) and the acute respiratory distress syndrome (ARDS) is to design and test interventions which reduce the incidence, severity, and complications of acute lung injury. We plan to approach this goal by performing multi- disciplinary research which will result in an improved understanding of the mechanisms of inflammation involved in acute lung injury and correlating this information with data on the clinical epidemiology of ARDS. We hypothesize that an imbalance in regulating factors differentiates lung inflammation which is a beneficial response to a foreign threat, self-limited and benign, from lung inflammation which does not resolve in the usual fashion and is injurious to tissue- "rogue" inflammation. We plan to study these factors and their effects in basic studies which involve animal models. In clinical studies we will explore this same phenomenon by studying elements of inflammation and their inhibitors in relation to endothelial and epithelial cells, correlated with clinical consequences. The approach of this SCOR proposal is multi-disciplinary. Research disciplines include cellular immunology and biology, biochemistry, physiology, morphology, and clinical epidemiology and biostatistics. The investigators have been trained in these investigative fields and are in the Departments of Medicine, Surgery, Pediatrics and Pathology of the School of Medicine and the Department of Health Services in the School of Public Health. This proposal is the result of a long and continuing interest in acute lung injury research by the investigators and is based on a strong history of productive collaboration among these investigators. Particular strengths of this proposal include the experience and productivity of the investigators in acute lung injury and inflammation- related research, the strong collaboration between clinical and basic science investigators, proven access to ALI and ARDS patient populations including patients with trauma and sepsis syndrome, and the existence of an established clinical data collection system and experience with an ALI and ARDS database.